This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this novel study is to elucidate the relationship between abnormalities in prefrontal structure and impairments in executive functioning by conducting a study of schizophrenia patients compared to controls using multi-modal magnetic resonance imaging (MRI) techniques. Background: Genes associated with vulnerability to schizophrenia may affect neurodevelopment and result in abnormalities in prefrontal structure and function. The prefrontal cortex occupies approximately one quarter of the human cortex and is part of the brain that is most unique to humans. It is the one of the last parts of the brain to mature, but is typically also the first part of the brain to suffer with age. The prefrontal cortex regulates executive processes such as attention, planning, judgment, impulse control, self-monitoring, and problem solving. Studies have demonstrated reduced prefrontal gray matter in schizophrenia patients and their healthy relatives compared to controls suggesting a genetic component (Cannon et al., 1998). In addition, problems in executive functioning are a fairly robust correlate of the schizophrenia diathesis (Snitz et al., 2006) and reduced prefrontal brain activity is also a reliable correlate of schizophrenia (Snitz et al., 2005). To date, most studies have analyzed structural and functional data in isolation. The purpose of this study is to examine the relationship between abnormalities in prefrontal cortical structure and BOLD response in schizophrenia patients, first-degree biological relatives of schizophrenia patients, and control subjects. We hypothesize that schizophrenia patients with prefrontal abnormalities in either structure or hemodynamic responses will have a similar regional abnormality in the complementary domain. Similar regional associations between structure and BOLD response will be observed in first-degree biological relatives of schizophrenia patients suggesting the abnormalities are related to the diathesis for schizophrenia. Covariation of structure and hemodynamic response will be less robust in control subjects.